Non-systemic control of parasites

ABSTRACT

Use of agonists and antagonists of the nicotinergic acetylcholine receptors of insects for the non-systemic control of parasitic insects, such as fleas, lice and flies, on humans and on animals.

This application is a division of U.S. Ser. No. 08/925,372, filed onSep. 8, 1997, now U.S. Pat. No. 6,232,328; which is a continuation ofU.S. Ser. No. 08/440,428, filed May 12, 1995, now abandoned.

The present invention relates to the non-systemic control of parasiticinsects on humans and animals by means of agonists or antagonists of thenicotinergic acetylcholine receptors in insects.

Agonists or antagonists of the nicotinergic acetylcholine receptors ofinsects are known. They include the nicotinyl insecticides, veryparticularly the chloronicotinyl insecticides. It is also known thatthese compounds have an outstanding action against plant-injuriousinsects. The systemic action of these compounds in plants against plant-injurious insects is also known.

PCT Application WO 93/24 002 discloses that certain1-[N-(halo-3-pyridylmethyl)-N-methylamino-1-alkylamino-2-nitroethylenederivatives are suitable for the systemic use against fleas on domesticanimals. In this type of application, the active compound isadministered orally or parenterally to the domestic animal, for exampleby means of an injection, thus entering the blood stream of the domesticanimal. The fleas then take up the active compound when they suck blood.WO 93/24 002 alleges that the non-systemic type of use is unsuitable forcontrolling fleas on domestic animals.

Surprisingly, it has now been found that these very agonists orantagonists of the nicotinergic acetylcholine receptors in insects areparticularly suitable for the non-systemic control of parasitic insectssuch as fleas, lice or flies on humans and animals. disclosed, forexample in European Offenlegungsschriften No. 464 830, 428 941, 425 978,386 565, 383 091, 375 907, 364 844, 315 826, 259 738, 254 859, 235 725,212 600, 192 060, 163 855, 154 178, 136 636, 303 570, 302 833, 306 696,189 972, 455 000, 135 956, 471 372, 302 389; GermanOffenlegungsschriften No. 3 639 877, 3 712 307; JapaneseOffenlegungsschriften No. 03 220 176, 02 207 083, 63 307 857, 63 287764, 03 246 283, 04 9371, 03 279 359, 03 255 072; U.S. Pat. Nos.5,034,524, 4,948,798, 4,918,086, 5,039,686, 5,034,404; PCT ApplicationsNo. WO 91/17 659, 91/4965; French Application No. 2 611 114; BrazilianApplication No. 88 03 621.

Reference is made expressly to the methods, processes, formulae anddefinitions described in these publications and to the individualpreparations and compounds described therein.

These compounds may preferably be represented by the general formula (I)

in which

R represents hydrogen, optionally substituted radicals from the groupconsisting of acyl, alkyl, aryl, aralkyl, heteroaryl or heteroarylalkyl;

A represents a monofunctional group from the series consisting ofhydrogen, acyl, alkyl and aryl, or represents a bifunctional group whichis linked to the radical Z;

E represents an electron-attracting radical;

X represents the radicals —CH═ or ═N—, it being possible for the radical—CH═ to be linked to the radical Z instead of an H atom;

Z represents a monofunctional group from the series consisting of alkyl,—O—R, —S—R and

or represents a bifunctional group which is linked to the radical A orthe radical X

Particularly preferred compounds of the formula (I) are those in whichthe radicals have the following meanings:

R represents hydrogen and optionally substituted radicals from theseries consisting of acyl, alkyl, aryl, aralkyl, heteroaryl andheteroarylalkyl.

Acyl radicals which may be mentioned are formyl, alkylcarbonyl,arylcarbonyl, alkylsulphonyl, arylsulphonyl or(alkyl)-(aryl-)-phosphoryl all of which may, in turn, be substituted.

Alkyl which may be mentioned is C₁₋₁₀-alkyl, in particular C₁₋₄-alkyl,specifically methyl, ethyl, i-propyl and sec- or t-butyl, all of whichcan, in turn, be substituted.

Aryl which may be mentioned is phenyl or naphthyl, in particular phenyl.

Aralkyl which may be mentioned is phenylmethyl or phenethyl.

Heteroaryl which may be mentioned is heteroaryl having up to 10 ringatoms and N, O, S, in particular N, as hetero atoms. The following maybe mentioned specifically: thienyl, furyl, thiazolyl, imidazolyl,pyridyl and benzothiazolyl.

Heteroarylalkyl which may be mentioned is heteroarylmethyl orheteroarylethyl having up to 6 ring atoms and N, O, S, in particular N,as heteroatoms.

The following substituents may be mentioned by way of example and asbeing preferred:

alkyl having preferably 1 to 4, in particular 1 or 2, carbon atoms, suchas methyl, ethyl, n- and i-propyl and n-, i- and t-butyl; alkoxy havingpreferably 1 to 4, in particular 1 or 2, carbon atoms, such as methoxy,ethoxy, n- and i-propyloxy and n-, i- and t-butyloxy; alkylthio havingpreferably 1 to 4, in particular 1 or 2, carbon atoms, such asmethylthio, ethylthio, n- and i-propylthio and n-, i- and t-butylthio;halogenoalkyl having preferably 1 to 4, in particular 1 or 2, carbonatoms and preferably 1 to 5, in particular 1 to 3, halogen atoms, thehalogen atoms being identical or different, and preferred halogen atomsbeing fluorine, chlorine or bromine, in particular fluorine, such astrifluoromethyl; hydroxyl; halogen, preferably fluorine, chlorine,bromine and iodine, in particular fluorine, chlorine and bromine; cyano;nitro; amino; monoalkyl- and dialkylamino having preferably 1 to 4, inparticular 1 or 2, carbon atoms per alkyl group, such as methylamino,methylethyl-amino, n- and i-propylamino and methyl-n-butylamino;carboxyl; carbalkoxy having preferably 2 to 4, in particular 2 or 3,carbon atoms such as carbomethoxy and carboethoxy; sulpho (—SO₃H);alkylsulphonyl having preferably 1 to 4, in particular 1 or 2, carbonatoms, such as methylsulphonyl and ethylsulphonyl; arylsulphonyl havingpreferably 6 or 10 aryl carbon atoms, such as phenylsulphonyl, and alsoheteroarylamino and heteroarylalkylamino, such as chloropyridylamino andchloropyridylmethylamino.

A particularly preferably represents hydrogen and also optionallysubstituted radicals from the series consisting of acyl, alkyl and aryl,all of which preferably have the meanings given in the case of R. Afurthermore represents a bifunctional group. The following group may bementioned: optionally substituted alkylene having 1-4, in particular1-2, C atoms, suitable substituents which may be mentioned being thoselisted further above and it being possible for the alkylene groups to beinterrupted by hetero atoms from the series consisting of N, O and S.

A and Z together with the atoms to which they are bonded can form asaturated or unsaturated heterocyclic ring. The heterocyclic ring cancontain a further 1 or 2 identical or different hetero atoms and/orhetero groups. Hetero atoms are preferably oxygen, sulphur or nitrogen,and hetero groups are N-alkyl, the alkyl of the N-alkl group preferablycontaining 1 to 4, in particular 1 or 2, carbon atoms. Alkyl which maybe mentioned is methyl, ethyl, n- and i-propyl and n-, i- and t-butyl.The heterocyclic ring contains 5 to 7, preferably 5 or 6, ring members.

Examples of the heterocyclic ring which may be mentioned arepyrrolidine, piperidine, piperazine, hexamethyleneimine,hexahydro-1,3,5-triazine and morpholine, all of which can optionally besubstituted, preferably by methyl.

E represents an electron-attracting radical, radicals which may bementioned being, in particular, NO₂, CN and halogenoalkylcarbonyl suchas 1,5-halogeno-C₁₋₄-cabonyl, in particular COCF₃.

x represents —C═ or —N═.

Z represents optionally substituted radicals alkyl, —OR, —SR and —NRR, Rand the substituents preferably having the abovementioned meaning.

Z can not only form the abovementioned ring, but can also, together withthe atom to which it is bonded and the radical

 instead of X form a saturated or unsaturated heterocyclic ring. Theheterocyclic ring can contain a further 1 or 2 identical or differenthetero atoms and/or hetero groups. Hetero atoms are preferably oxygen,sulphur or nitrogen, and hetero groups are N-alkyl, the alkyl or N-alkylgroup preferably containing 1 to 4, in particular 1 or 2, carbon atoms.Alkyl which may be mentioned is methyl, ethyl, n- and i-propyl and n-,i- and t-butyl. The heterocyclic ring contains 5 to 7, preferably 5 or6, ring members.

Examples of the heterocyclic ring which may be mentioned arepyrrolidine, piperidine, piperazine, hexamethyleneimine; morpholine andN-methylpiperazine.

The compounds of the general formulae (II) and (III) may be mentioned ascompounds which can be used very particularly preferably according tothe invention:

in which

n represents 1 or 2,

Subst. represents one of the abovementioned substituents, in particularhalogen, very particularly chlorine, and

A, Z, X and E have the abovementioned meanings.

The following compounds may be mentioned specifically:

The active compounds are suitable for the control of parasitic insectswhich can be found in humans and in animal keeping and livestockbreeding in domestic animals, productive livestock, zoo animals,laboratory animals, experimental animals and pets, while havingfavourable toxicity to warm-blooded species. They are active against allor individual development stages of the pests and against resistant andnormally sensitive pest species.

The pests include:

From the order of the Anoplura, for example, Haematopinus spp.,Linognathus spp., Solenopotes spp., Pediculus spp., Pthirus spp;

From the order of the Mallophaga, for example, Trimenopon spp., Menoponspp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicolaspp., Damalinea spp., Bovicola spp;

From the order of the Diptera, for example, Chrysops spp., Tabanus spp.,Musca spp., Hydrotaea spp., Muscina spp., Haematobosca spp., Haematobiaspp., Stomoxys spp., Fannia spp., Glossina spp., Lucilia spp.,Calliphora spp., Auchmeromyia spp., Cordylobia spp., Cochliomyia spp.,Chrysomyia spp., Sarcophaga spp., Wohlfartia spp., Gasterophilus spp.,Oesteromyia spp., Oedemagena spp., Hypoderma spp., Oestrus spp.,

Rhinoestrus spp., Melophagus spp., Hippobosca spp.

From the order of the Siphonaptera, for example, Ctenocephalides spp.,Echidnophaga spp., Ceratophyllus spp.

Particular mention may be made of the action against Siphonaptera, inparticular against fleas.

Particularly mentioned are the following animals.

The productive livestock and breeding animals include mammals such as,for example, cattle, horses, sheep, pigs, goats, camels, water buffalo,donkeys, rabbits, fallow deer, reindeer, fur-bearing animals such as,for example, mink, chinchilla, racoon, birds such as, for example,chickens, geese, turkeys and ducks.

Laboratory and experimental animals include mice, rats, guinea pigs,golden hamsters, dogs and cats.

Pets include dogs and cats.

Administration can be effected prophylactically as well astherapeutically.

The active compounds are administered, directly or in the form ofsuitable preparations, dermally, by environment treatment, or with theaid of active-compound-containing shaped articles such as, for example,strips, plates, bands, collars, ear marks, limb bands, marking devices.

Dermal administration is effected, for example, in the form of bathing,dipping, spraying, pouring on, spotting on, washing, shampooing, pouringover, and dusting.

Suitable preparations are:

solutions or concentrates for administration after dilution, solutionsfor use on the skin, pour-on and spot-on formulations, gels;

emulsions and suspensions for dermal administration, and semi-solidpreparations;

formulations in which the active compound is incorporated into a creambase or into an oil-in-water or water-in-oil emulsion base;

solid preparations such as powders, or shaped articles containing activecompound.

Solutions for use on the skin are applied dropwise, brushed on, rubbedin, sprayed on, splashed on, or applied by dipping, bathing or washing.

The solutions are prepared by dissolving the active compound in asuitable solvent and, if appropriate, adding additives such assolubilizers, acids, bases, buffer salts, antioxidants andpreservatives.

The following may be mentioned as solvents: physiologically acceptablesolvents such as water, alcohols such as ethanol, butanol, benzylalcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols,N-methyl-pyrrolidone, and mixtures of these.

If appropriate, the active compounds can also be dissolved inphysiologically acceptable vegetable or synthetic oils.

The following may be mentioned as solubilizers: solvents which enhancesolution of the active compound in the main solvent, or which preventits precipitation. Examples are polyvinylpyrrolidone, polyoxyethylatedcastor oil, polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoicesters, n-butanol.

It may be advantageous to add thickeners during the preparation of thesolutions. Thickeners are: inorganic thickeners such as bentonites,colloidal silica, aluminium monostearate, organic thickeners such ascellulose derivatives, polyvinyl alcohols and their copolymers,acrylates and methacrylates.

Gels, which are applied to, or brushed onto, the skin, are prepared bytreating solutions which have been prepared as described above with suchan amount of thickener that a clear substance of cream-like consistencyis formed. Thickeners applied are the thickeners indicated furtherabove.

Pour-on and spot-on formulations are poured or sprayed onto limitedareas of the skin, the active compound spreading on the body surface.

Pour-on and spot-on formulations are prepared by dissolving, suspendingor emulsifying the active compound in suitable solvents or solventmixtures which are tolerated by the skin. If appropriate, otheradjuvants such as colorants, antioxidants, light stabilizers andtackifiers are added.

Solvents which may be mentioned are: water, alkanols, glycols,polyethylene glycols, polypropylene glycols, glycerol, aromatic alcoholssuch as benzyl alcohol, phenylethanol, phenoxyethanol, esters such asethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkyleneglycol alkyl ethers, such as dipropylene glycol monomethyl ether,diethylene glycol mono-butyl ether, ketones such as acetone, methylethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable orsynthetic oils, DMF, dimethylacetmide, N-methylpyrrolidone,2-dimethyl-4-oxy-methylene-1,3-dioxolane.

Colorants are all colorants which are licensed for use on animals andwhich can be dissolved or suspended.

Adjuvants are also spreading oils such as isopropyl myristate,dipropylene glycol pelargonate, silicone oils, fatty acid esters,triglycerides and fatty alcohols.

Antioxidants are sulphites or metabisulphites such as potassiummetabisulphite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisoleand tocopherol.

Examples of light stabilizers are substances from the benzophenoneclass, or novantisolic acid.

Examples of tackifiers are cellulose derivatives, starch derivatives,polyacrylates, natural polymers such as alginates, gelatin.

Emulsions are either of the water-in-oil type or of the oil-in-watertype.

They are prepared by dissolving the active compound either in thehydrophobic or in the hydrophilic phase and homogenizing this phase withthe solvent of the other phase, with the aid of suitable emulsifiersand, if appropriate, other adjuvants such as colorants, absorptionaccelerators, preservatives, antioxidants, light stabilizers,viscosity-increasing substances.

The following may be mentioned as the hydrophobic phase (oils): paraffinoils, silicone oils, natural vegetable oils such as sesame seed oil,almond oil, castor oil, synthetic triglycerides such as caprylic/capricacid biglyceride, triglyceride mixture with vegetable fatty acids ofchain length C₈₋₁₂ or with other specifically selected natural fattyacids, partial glyceride mixtures of saturated or unsaturated fattyacids which may also contain hydroxyl groups, and mono- and diglyceridesof the C₈/C₁₀-fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyllaurate, dipropylene glycol pelargonate, esters of a branched fatty acidof medium chain length with saturated fatty alcohols of chain lengthC₁₆-C₁₈, isopropyl myristate, isopropyl palmitate, caprylic/capricesters of saturated fatty alcohols of chain length C₁₂-C₁₈, isopropylstearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxyfatty acid esters such as dibutyl phthalate, diisopropyl adipate, estermixtures related to the latter, and other fatty alcohols such asisotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol and oleylalcohol.

Fatty acids such as, for example, oleic acid and its mixtures.

The following may be mentioned as the hydrophilic phase: water, alcoholssuch as, for example, propylene glycol, glycerol, sorbitol and theirmixtures.

The following may be mentioned as emulsifiers: non-ionic surfactants,for example polyoxyethylated castor oil, polyoxyethylated sorbitanmonooleate, sorbitan monostearate, glycerol monostearate, polyoxyethylstearate, alkylphenol polyglycol ethers;

ampholytic surfactants such as di-sodium N-lauryl-β-iminodipropionate orlecithin;

anionic surfactants such as Na lauryl sulphate, fatty alcohol ethersulphates, the monoethanolamine salt of mono/dialkyl polyglycol etherorthophosphoric esters;

cationic surfactants such as cetyltrimethylammonium chloride.

The following may be mentioned as other adjuvants: viscosity-increasingsubstances and substances which stabilize the emulsion, such ascarboxymethylcellulose, methylcellulose and other cellulose and starchderivatives, polyactylates, alginates, gelatin, gum arabic,polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinylether and maleic anhydride, polyethylene glycols, waxes, colloidalsilica, or mixtures of the substances mentioned.

Suspensions are prepared by suspending the active compound in anexcipient liquid, if appropriate with an addition of further adjuvantssuch as wetting agents, colorants, absorption accelerators,preservatives, antioxidants and light stabilizers.

Excipient liquids which may be mentioned are all homogeneous solventsand solvent mixtures.

Wetting agents (dispersants) which may be mentioned are the surfactantsindicated further above.

Further adjuvants which may be mentioned are those indicated furtherabove.

Semi-solid preparations for dermal administration are only distinguishedfrom the above-described suspensions and emulsions by their higherviscosities.

To prepare solid preparations, the active compound is mixed withsuitable carriers, if appropriate with the addition of adjuvants, andthe mixture is formulated as desired.

Carriers which may be mentioned are all physiologically acceptable solidinert substances. Suitable as such are inorganic and organic substances.Examples of inorganic substances are sodium chloride, carbonates such ascalcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays,precipitated or colloidal silicon dioxide, and phosphates.

Adjuvants are preservatives, antioxidants and colorants which havealready been indicated further above.

Other suitable adjuvants are lubricants and glidants such as, forexample, magnesium stearate, stearic acid, talc and bentonites.

Ready-to-use preparations contain the active compound in concentrationsfrom 1 ppm-20 per cent by weight, preferably 0.01-10 per cent by weight.

Preparations which are diluted prior to use contain the active compoundin concentrations of 0.5-19 per cent by weight, preferably 1 to 50 percent by weight.

In general, it has proved advantageous to administer amounts ofapproximately 0.5 to approximately 50 mg, preferably 1 to 20 mg, ofactive compound per kg of body weight per day, to achieve effectiveresults.

Particular mention may be made of the use via shaped articles. Shapedarticles are, inter alia, collars, attachments for collars (medallions),ear tags, bands which are affixed to limbs or parts of the body,adhesive strips and films, and peel-off films

Particular mention may be made of collars and medallions.

Suitable polymers for the preparation of the shaped articles arethermoplastic and flexible, heat-curable polymers and also elastomersand thermoplastic elastomers. Polymers which may be mentioned arepolyvinyl resins, polyurethanes, polyacrylates, epoxy resins, cellulose,cellulose derivatives, polyamides and polyesters which are sufficientlycompatible with the abovementioned active compound. The polymers must besufficiently strong and flexible so as not to tear or become brittleupon shaping. They must be sufficiently stable so as to be resistant tonormal wear and tear. Moreover, the polymers must allow sufficientmigration of the active compound towards the surface of the shapedarticle.

Other polyvinyl resins include polyvinyl halides such as polyvinylchloride, polyvinyl chloride/vinyl acetate and polyvinyl fluoride;polyacrylate and polymethacrylate esters, such as polymethyl acrylateand polymethyl methacrylate; and polyvinylbenzenes, such as polystyreneand polyvinyltoluene. Particular mention may be made of polyvinylchloride.

Plasticizers which a re suitable for the preparation of thepolyvinyl-resin-based shaped articles are those which are conventionallyused for plasticizing solid vinyl resins. The choice of plasticizer tobe used depends on the resin and its compatibility with the plasticizer.Examples of suitable plasticizers are esters of phosphoric acid, such asesters of phthalic acid, such as dimethyl phthalate and dioctylphthalate, and esters of adipic acid, such as diisobutyl adipate. It isalso possible to use other esters, such as the esters of azelaic acid,maleic acid, ricinoleic acid, myristic acid, palmitic acid, oleic acid,sebacic acid, stearic acid and trimellithic acid, as well as complexlinear polyesters, polymeric plasticizers and epoxidized soyabean oils.The quantity of the plasticizer amounts to approximately 10 to 50% byweight preferably approximately 20 to 45% by weight of the entirecomposition.

The shaped articles may furthermore comprise other constituents such asstabilizers, lubricants, fillers and colorants, without this alteringthe basic characteristics of the composition. Suitable stabilizers areantioxidants and agents which protect the bands against ultravioletradiation and undesirable degradation during working, such as extruding.Moreover, some stabilizers, such as epoxidize soya bean oils, also actas secondary plasticizers. Examples of lubricants which can be used arestearnates, stearic acid and low-molecular-weight polyethylenes. Thesecomponents may be used in a concentration of up to approximately 5% byweight of the entire composition.

When preparing the vinyl-based shaped articles, the various componentsare mixed by known processes and subjected to compression moulding byknown extruding or injection moulding processes.

From the technical point of view, the choice of the processing processfor the preparation of the shaped articles depends essentially on therheological properties of the band material and the shape of the banddesired. The processing processes can be adjusted to suit the processingtechnology or the type of shaping. In the processing technology, theprocesses may be classified according to the rheological states whichpass through them. Accordingly, suitable processes for viscose materialsfor bands are casting, compressing, injection moulding and applying, andsuitable processes for elastoviscose polymers are injection moulding,extruding (extrusion moulding), calendering, rolling and, ifappropriate, edging. Classified by the type of shaping, the shapedarticles according to the invention may be prepared by casting,immersing, compressing, injection moulding, extruding, calendering,stamping, bending, thermoforming and the like.

These processing processes are known and need no further explanation. Inprinciple, the illustrations given above by way of example for polyvinylresins also apply to other polymers.

The polyurethanes acting as carrier material are prepared in a mannerknown per se by reacting polyisocyanates having high-molecular-weightcompounds with at least two groups capable of reacting with isocyanates,and, if appropriate, low-molecular-weight chain extenders and/ormonofunctional chain terminators.

Suitable starting components for the preparation of the polyurethanesare aliphatic, cycloaliphatic, araliphatic, aromatic and heterocyclicpolyisocyanates, as they are described, for example, by W. Siefken inLiebig's Annalen der Chemie, 562, pages 75 to 136. The following may bementioned by way of example: ethylene diisocyanate, 1,4-tetramethylenediisocyanate, 1,6-hexamethylene diisocyanate, 1,12-dodecanediisocyanate, cyclobutane 1,3-diisocyanate, cyclohexane 1,3-diisocyanateand cyclohexane 1,4-diisocyanate and any desired mixtures of thesecompounds, 1-isocyanato-3,3,5. -trimethyl-5-isocyanatomethyl-cyclohexane(see DE-AS (German Published Specification) 202 785 and U.S. Pat. No.3,401,190), 2,4- and 2,6-hexahydrotoluylene diisocyanate and any desiredmixtures of these compounds; hexahydro-1,3- and/or -1,4-phenylenediisocyanate, perhydro-2,4′- and/or -4,4′-diphenylmethane diisocyanate,1,3- and 1,4-phenylene diisocyanate, 2,4- and 2,6-toluylene diisocyanateand any desired mixtures of these compounds; diphenylmethane2,4′-diisocyanate and/or diphenylmethane 4,4′-diisocyanate, naphthylene1,5-diisocyanate, triphenylmethane 4,4′, 4″-triisocyanate,polyphenyl-polymethylene polyisocyanates as they are obtained byaniline/formaldehyde condensation followed by phosgenation anddescribed, for example, in GB Patent Specifications 874 430 and 848 671;m- and p-isocyanatophenol-sulphonyl isocyanates in accordance with U.S.Pat. Nos. 3,454,606; perchlorinated aryl polyisocyanates as they aredescribed, for example, in DE-AS (German Published Specification)1,157,601 and in U.S. Pat. No. 3,277,138; polyisocyanates havingcarbodiimide groups, as they are described in German PatentSpecification 1 092 007 and in U.S. Pat. No. 3,152,162; diisocyanates asthey are described in U.S. Pat. No. 3,492,330; polyisocyanates havingallophanate groups as they are described, for example, in British PatentSpecification 994 890, German Patent Specification 761 626 and thepublished Dutch Patent Application 7 102 524; polyisocyanates havingisocyanurate groups, as they are described, for example, in U.S. Pat.No. 3,001,973, in German Patent Specifications 1 022 789, 1 222 067 and1 027 394 and in DE-OS (German Published Specifications) 1 929 034 and 2004 048; polyisocyanates having urethane groups, as they are described,for example, in German Patent Specification 752 261 or in U.S. Pat. No.3,394,164; polyisocyanates having acylated urea groups, in accordancewith German Patent Specification 1 230 778; polyisocyanates havingbiuret groups, as they are described, for example, in German PatentSpecification 1 101 394, in U.S. Pat. Nos. 3,124,605 and 3,201,372, andin British Patent Specification 889 050; polyisocyanates prepared bytelomerization reactions, as they are described, for example, in U.S.Pat. No. 3,654,106; polyisocyanates having ester groups, as they arementioned in, for example, British Patent Specifications 965 474 and 1072 956, in U.S. Pat. No. 3,567,763 and in German Patent Specification 1231 688; reaction products of the abovementioned isocyanates withacetals in accordance with German Patent Specification 1 072 385, andpolyisocyanates containing polymeric fatty acid radicals, in accordancewith U.S. Pat. No. 3,455,883.

It is also possible to employ the distillation residues which haveisocyanate groups and which are obtained in the preparation ofisocyanate on a technical scale, if appropriate dissolved in one or moreof the abovementioned polyisocyanates. It is furthermore possible toemploy any desired mixtures of the abovementioned polyisocyanates.

Preferred polyisocyanates are, in general, the toluylene diisocyanatesand the diphenylmethane diisocyanates.

Starting components for the preparation of the polyurethanes arefurthermore compounds of a molecular weight of, as a rule, 400-10,000which have at least two hydrogen atoms which are reactive towardsisocyanates. Besides compounds which have amino groups, thiol groups orcarboxyl groups, these are preferably to be understood as meaningpolyhydroxyl compounds, in particular compounds having two to eighthydroxyl groups, specifically those of a molecular weight of 800 to10,000, preferably 1,000 to 6,000, for example polyesters, polyethers,polythioethers, polyacetals, polycarbonates and polyester amides havingat least two, as a rule 2-8, but preferably 2-4, hydroxyl groups, asthey are known per se for the preparation of homogeneous and cellularpolyurethanes.

Examples of suitable polyesters having hydroxyl groups are reactionproducts of polybasic, preferably dibasic and, if appropriate,additionally tribasic, carboxylic acids. Instead of the freepolycarboxylic acids, it is also possible to use the correspondingpolycarboxylic anhydrides or the corresponding polycarboxylates of loweralcohols or their mixtures for preparing the polyesters. Thepolycarboxylic acids can be of aliphatic, cycloaliphatic, aromaticand/or heterocyclic nature and can optionally be substituted, forexample by halogen atoms, and/or unsaturated.

Examples which may be mentioned are: succinic acid, adipic acid, subericacid, azelaic acid, sebacic acid, phthalic acid, isophthalic acid,trimellitic acid, phthalic anhydride, tetrahydrophthalic anhydride,hexahydrophthalic anhydride, tetrachlorophthalic anhydride,endomethylenetetrahydrophthalic anhydride, glutaric anhydride, maleicacid, maleic anhydride, fumaric acid, dimeric and trimeric fatty acidssuch as oleic acid, if appropriate as a mixture with monomeric fattyacids, dimethyl terephthalate and terephthalic acid bis-glycol ester.

Examples of suitable polyhydric alcohols are ethylene glycol,propylene-1,2- and -1,3-glycol, butylene-1,4- and -2,3-glycol,hexane-1,6-diol, octane-1,8-diol, neopentyl glycol,cyclohexanedimethanol(1,4-bis-hydroxy-methylcyclohexane),2-methyl-1,3-propanediol, glycerol, trimethylolpropane,hexane-1,2,6-triol, butane-1,2,4-triol, trimethylethane,pentaerythritol, quinitol, mannitol and sorbitol, methylglycositol,furthermore diethylene glycol, triethylene glycol, tetraethylene glycol,polyethylene glycols, dipropylene glycol, polypropylene glycols,dibutylene glycol and polybutylene glycols. The polyesters mayproportionately have terminal carboxyl groups. Polyesters of lactones,for example ε-caprolactone, or hydroxycarboxylic acids, for exampleω-hydroxycaproic acid, may also be employed.

Suitable polyhydric alcohols are polyethers which have at least two, asa rule two to eight, preferably two to three, hydroxyl groups. These areknown per se and are prepared, for example, by polymerizing epoxides,such as ethylene oxide, propylene oxide, butylene oxide,tetrahydrofuran, styrene oxide or epichlorohydrin, with themselves, forexample in the presence of BF₃, or by an addition reaction of theseepoxides, if appropriate as a mixture or in succession, with startingcomponents having reactive hydrogen atoms, such as water, alcohols,ammonia or amines, for example ethylene glycol, propylene-1,3-glycol orpropylene-1,2-glycol, trimethylolpropane, 4,4′-dihydroxydiphenylpropane, aniline, ethanolamine or ethylenediamine. Othersuitable substances are sucrose polyethers as they are described, forexample, in DE-AS (German Published Specifications) 1 176 358 and 1 064938. Frequently, those polyethers which have predominantly (up to 90% byweight based on all OH groups present in the polyether) primary OHgroups are preferred. Other suitable substances are polyethers which aremodified by vinyl polymers, as they are formed, for example, bypolymerizing styrene and acrylonitrile in the presence of polyethers(U.S. Pat. Nos. 3,383,351, 3,304,273, 3,523,093, 3,110,695, GermanPatent Specification 1 152 36), as are polybutadienes having OH groups.

Amongst the polythioethers, particular mention may be made of thecondensation products of thiodiglycol with itself and/or with otherglycols, dicarboxylic acids, formaldehyde, aminocarboxylic acids oramino alcohols. Depending on the components, the products are mixedpolythioethers, or polythioetherates or polythioetheramidates.

Suitable polyacetals are, for example, those compounds which can beprepared from glycols, such as diethylene glycol, triethylene glycol,4,4′-dioxethoxydiphenyl-dimethylmethane, hexanediol and formaldehyde.Polyacetals which are suitable according to the invention may also beprepared by polymerizing cyclic acetals.

Suitable polycarbonates having hydroxyl groups are those of the typeknown per se, which can be prepared, for example, by reacting diols,such as propane-1,3-diol, butane-1,4-diol and/or hexane-1,6-diol,diethylene glycol, triethylene glycol or tetraethylene glycol, withdiaryl carbonates, for example diphenyl carbonate, or phosgene.

The polyamidates and polyamides include, for example, the predominantlylinear condensates obtained from polybasic saturated and unsaturatedcarboxylic acids or their anhydrides and polyhydric saturated andunsaturated amino alcohols, diamines, polyamines and their mixtures.

Other substances which can be used are polyhydroxyl compounds whichalready have urethane or urea groups, as well as optionally modifiednatural polyols, such as castor oil, or carbohydrates or starch. Othersubstances which can be employed according to the invention are additionproducts of alkylene oxides with phenol/formaldehyde resins or else withurea/formaldehyde resins.

Representatives of these compounds are described, for example, in HighPolymers, Vol. XVI, “Polyurethans, Chemistry and Technology”, bySaunders-Frisch, Interscience Publishers, New York, London, Volume I,1962, pages 32-42 and pages 44-54 and Volume II, 1964, pages 5-6 and198-199, and in Kunststoff Handbuch [Plastics Manual], Volume VII,Vieweg Höchtlen, Carl-Hanser-Verlag, Munich, 1966, for example on pages45-71.

Naturally, it is possible to employ mixtures of the abovementionedcompounds of a molecular weight of 400-10,000 which have at least twohydrogen atoms which are reactive towards isocyanates, for example inthe form of polyether mixtures.

Other suitable starting components to be employed, if appropriate, arecompounds of a molecular weight of 32-400 which have at least twohydrogen atoms which are reactive towards isocyanates. In this case too,such compounds are understood as meaning compounds having hydroxylgroups and/or amino groups and/or thiol groups and/or carboxyl groups,preferably compounds which act as chain extenders or crosslinkingagents.

These compounds have, as a rule 2 to 8 hydrogen which are reactivetowards isocyanates, preferably 2 or 3 reactive hydrogen atoms.

Examples of such compounds which may be mentioned are:

ethylene glycol, propylene-1,2- and -1,3-glycol, butylene-1,4- and-2,3-glycol, pentane-1,5-diol, hexane-1,8-diol, octane-1,8-diol,neopentyl glycol, 1,4-bis-hydroxymethyl-cyclohexane,2-methyl-1,3-propanediol, glycerol, trimethylolpropane,hexane-1,2,6-triol, trimethylolethane, pentaerythritol, quinitol,mannitol and sorbitol, diethylene glycol, triethylene glycol,tetraethylene glycol, polyethylene glycols having a molecular weight ofup to 400, dipropylene glycol, polypropylene glycols having a molecularweight of up to 400, dibutyllene glycol, polybutylene glycols having amolecular weight of up to 400, 4,4′-dihydroxy-diphenylpropane,di-hydroxymethylhydroquinone, ethanolamine, diethanolamine,triethanolamine, 3-aminopropanol, ethylenediamine, 1,3-diaminopropane,1-mercapto-3-aminopropane, 4-hydroxy- or -amino-phthalic acid, succinicacid, adipic acid, hydrazine, N,N′-dimethylhydrazine,4,4′-diaminodiphenylmethane, toluylenediamine,methylene-bis-chloroaniline, methylene-bis-anthrailates,diaminobenzoates and the isomeric chlorophenylene-diamines.

In this case too, mixtures of various compounds of a molecular weight of32-400 having at least two hydrogen atoms which are reactive towardsisocyanates may be used.

However, it is also possible to employ polyhydroxyl compounds whichcontain high-molecular-weight polyadducts or polycondensates in finelydisperse or dissolved form. Such modified polyhydroxyl compounds areobtained when polyaddition reactions (for example reactions betweenpolyisocyanates and amino-functional compounds) or polycondensationreactions (for example between formaldehyde and phenols and/or amines)are allowed to proceed directly in situ in the abovementioned compoundshaving hydroxyl groups. Such processes are described, for example, inDE-AS (German Published Specifications) 1 168 075 and 1 260 142 and inDE-OS (German Published Specifications) 2 324 134, 2 423 984, 2 512 385,2 513 815, 2 550 797, 2 550 833 and 2 550 862. However, it is alsopossible, in accordance with U.S. Pat. No. 3,869,413 or DE-OS (GermanPublished Specification) 2 550 860 to mix a finished aqueous polymerdispersion with a polyhydroxyl compound and subsequently to remove thewater from the mixture.

When selecting the higher-molecular-weight polyol component used for thepreparation of the polyurethane, it must be borne in mind that thefinished polyurethane should not be capable of swelling in water. Thus,using an excess of polyhydroxyl compounds having ethylene oxide units(polyethylene glycol polyethers or polyesters having diethylene glycolor triethylene glycol as diol component) is therefore to be avoided.

Substances which may be particularly emphasized for the preparation ofthe shaped articles are thermoplastic elastomers. These are materialswhich comprise elastomeric phases either mixed physically or bondedchemically in polymers which can be processed as thermoplastics. Adistinction is made between polyblends, in which the elastomeric phasesare a component of the polymeric matrix. Hard and soft regions arepresent side by side as a result of the build-up of the thermoplasticelastomers. The hard regions form a crystalline network structure or acontinuous phase, the interstices of which are filled by elastomericsegments. Due to this build-up, these materials have rubber-likeproperties.

A distinction is made between 5 main groups of thermoplastic elastomers:

1. Copolyesters

2. Polyether block amides (PEBA)

3. Thermoplastic polyurethanes (TPU)

4. Thermoplastic polyolefins (TPO)

5. Styrene block copolymers

Suitable copolymers (segmented polyester elastomers) are built up, forexample, from a large number of recurring, short-chain ester units andlong-chain ester units, which are combined by ester bonds, theshort-chain ester units making up about 15-65% by weight of thecopolyester and having the formula I.

in which

R represents a divalent radical of a dicarboxylic acid having amolecular weight of less than about 350, and

D represents a divalent radical of an organic diol having a molecularweight of less than about 250,

The long-chain ester units make up about 35-85% by weight of thecopolyester and have the formula E

in which

R represents a divalent radical of a dicarboxylic acid having amolecular weight of less than about 350, and

G represents a divalent radical of a long-chain glycol having an averagemolecular weight of about 350 to 6000.

The copolyesters which can be used according to the invention can beprepared by polymerizing with one another a) one or more dicarboxylicacids, b) one or more linear, long-chain glycols and c) one or morelow-molecular-weight diols.

The dicarboxylic acids for the preparation of the copolyester can bearomatic, aliphatic or cycloaliphatic. The preferred dicarboxylic acidsare the aromatic acids having 8-16 C atoms, in particularphenylenedicarboxylic acids, such as phthalic, terephthalic andisophthalic acid.

The low-molecular-weight diols for the reaction to form the short-chainester units of the copolyesters belong to the classes of acyclic,alicyclic and aromatic dihydroxy compounds. The preferred diols have2-15 C atoms, such as ethylene glycol, propylene glycol, tetraethyleneglycol, isobutylene glycol, pentamethylene glycol,2,2-dimethyltrimethylene glycol, hexamethylene glycol and decamethyleneglycol, dihydroxycyclohexane, cyclohexanedimethanol, resorcinol,hydroquinone and the like. The bisphenols for the present purposeinclude bis-(hydroxy)-iphenyl, bis-(p-hydroxyphenyl)methane,bis-(p-hydroxyphenyl)-ethane and bis-(hydroxyphenyl)-propane.

The long-chain glycols for the preparation of the soft segments of thecopolyesters preferably have molecular weight of about 600 to 3000. Theyinclude poly(alklyleneether) glycols in which the alkylene groups have2-9 carbon atoms.

Glycol esters of poly-(alkyleneoxide)-dicarboxylic acids can also beused as the long-chain glycol.

Polyester glycols can also be used as the long-chain glycol.

The long-chain glycols also include polyformals, which are obtained byreaction of formaldehyde with glycols. Polythioether glycols are alsosuitable. Polybutadiene glycols and polyisoprene glycols, copolymersthereof and saturated hydrogenation products of these materials aresatisfactory long-chain polymeric glycols.

Processes for the synthesis of such copolyesters are disclosed in DOS[German Published Specification) 2 239 271, DOS (Getman PublishedSpecification) 2 213 128, DOS (German Published Specification) 2 449 343and U.S. Pat. No. 3,023,192.

Suitable copolyesters are obtainable, for example, under the trade names®Hytrel from Du Pont, ®Pelpren from Toyobo®, Arnitel from Akzo, ®Ectelfrom Eastman Kodak and ®Riteflex from Hoechst.

Suitable polyether block amides are, for example, those composed ofpolymer chains which are built up from recurrent units, corresponding tothe formula I.

in which

A is the polyamide chain derived from a polyamide having 2 terminalcarboxyl groups by loss of the latter,

B is the polyoxyalkylene glycol chain derived from a polyoxyalkyleneglycol having terminal OH groups by loss of the latter, and

n is the number of units forming the polymer chain.

The end groups are preferably OH groups or radicals of compounds whichterminate the polymerization.

The dicarboxylic polyamides having terminal carboxyl groups are obtainedin a known manner, for example by polycondensation of one or morelactams or/and one or more amino acid, furthermore by polycondensationof a dicarboxylic acid with an amine, in each case in the presence of anexcess of an organic dicarboxylic acid, preferably having terminalcarboxyl groups. During the polycondensation, these carboxylic acidsbecome a component of the polyamide chain and become attached inparticular to the end of this polyamide chain, resulting in anα-ω-dicarboxylic polyamide. The dicarboxylic acid furthermore acts as achain terminator, which is why it is also employed in an excess.

The polyamide can be obtained starting from lactams and/or amino acidshaving a hydrocarbon chain composed of 4-14 C atoms, such as, forexample, caprolactam, oenantholactam, dodecalactam, undecanolactam,decanolactam, 11-amino-undecano or 12-aminododecanoic acid.

Examples which may be mentioned of polyamides, as they are formed bypolycondensation of a dicarboxylic acid with a diamine, are thecondensation products of hexamethylenediamine with adipic acid, azelaicacid, sebacic acid and 1,12-dodecanedioic acid, and the condensationproducts of nonamethylenediamine and adipic acid.

Suitable as dicarboxylic acid used for the synthesis of the polyamide,that is to say, on the one hand, for fixing in each case one carboxylgroup at each end of the polyamide chain and, on the other hand, aschain terminator, are those having 4-20 C atoms, in particularalkanedioic acids, such as succinic acid, adipic acid, suberic acid,azelaic acid, sebacic acid, undecanedioic or dodecanedioic acid,furthermore cycloaliphatic or aromatic dicarboxylic acid, such asterephthalic acid, isphthalic acid or cyclohexane-1,4-dicarboxylic acid.

The polyoxyalkylene glycols having terminal OH groups are unbranched orbranched and have an alkylene radical having at least 2 C atoms. Theyare, in particular, polyoxyethylene glycol, polyoxypropylene glycol andpolyoxytetramethylene glycol, and their copolymers.

The average molecular weight of these polyoxyalkylene glycols which areterminated by OH groups may vary within a wide range, it isadvantageously between 100 and 6000, in particular between 200 and 3000.

The amount by weight of the polyoxyalkylene glycol, based on the totalweight of polyoxyalkylene glycol and dicarboxylic polyamide used for thepreparation of the PEBA polymer, is 5-85%, preferably 10-50%

Processes for the synthesis of such PEBA polymers are disclosed inFrench Patent Specification 7 418 913 (Publication No. 2 273 021), DOS(German Published Specification) 2 802 989, DOS (German PublishedSpecification) 2 837 687, (German Published Specification) 2 523 991,EP-S (European Published Specification) 0 095 893, DOS (German PublishedSpecification) 2 712 987 and DOS (German Published Specification) 2 716004.

Preferably suitable PEBA polymers are those which, in contrast to thosedescribed above, have random structure. To prepare these polymers, amixture of

1. one or more polyamide-forming compounds from the group of theω-aminocarboxylic acids or lactams having at least 10 carbon atoms,

2. an α-ω-aminodihydroxy-polyoxyalkylene glycol,

3. at least one organic dicarboxylic acid

in a ratio by weight of 1:(2+3) between 30:70 and 98:2, where equivalentamounts of hydroxyl and carbonyl groups are present in (2+3), is heatedin the presence of 2 to 30 per cent by weight of water, based on thepolyamide-forming compounds of the group 1, under the inherent pressurewhich is established at temperatures of between 23° C. and 30° C., andsubsequently, after the water has been removed, reacted further underatmospheric pressure or under reduced pressure at 250 to 280° C. withthe exclusion of oxygen.

Such PEBA polymers which are preferably suitable are described, forexample, in DE-OS (Geman Published Specification) 2 712 987.

PEBA polymers which are suitable and preferably suitable can beobtained, for example, under the trade names ®PEBAX by Atochem,®Vestarid by Hüls AG, ®Grilamid by EMS-Chemie and ®Kellaflex by DSM.

The shaped articles comprise active compound concentrations of 1 to 20%by weight, preferably 5 to 20% by weight, particularly preferably around10% by weight.

In the case of collars, the active compound concentrations arepreferably 1 to 15%, in the case of medallions, pendants and ear tagspreferably 5 to 20%, in the case of films and adhesive strips preferably0.1 to 5%.

In the preparations and shaped articles, the active compounds can bepresent in the form of a mixture with synergists or other activecompounds. The active compounds include insecticides, such as phosphoricor phosphonic acid esters, natural or synthetic pyrethroids,carbarnates, amidines, juvenile hormones and juvenoid synthetic activecompounds.

The phosphoric or phosphoric acid esters include:

0-ethyl-0-(8-quinolyl) phenyl-thiophosphate (quintiofos),

0,0-diethyl 0-(3-chloro-4-methyl-7-coumarinyl) thiophosphate(coumaphos),

0,0-diethyl 0-phenylglyoxylonitrile oxime thiophosphate (phoxim),

0,0-diethyl 0-cyanochlorobenzaldoxime thiophosphate (chlorphoxim),

0,0-diethyl 0-(4-bromo-2,5-dichlorophenyl) phosphorothionate(bromophos-ethyl),

0,0,0′,0′-tetraethyl-S,S′-methylene di(phosphorodithionate) (ethion),

2,3-p-dioxanedithiol-S,S-bis(0,0-diethyl phosphorodithionate,

2-chloro-1-(2,4-dichlorophenylyvinyl diethyl phosphate(chlorfenvinphos),

0,0-dimethyl 0-(3-methyl-4-methylthiophenyl) thionophosphate (fenthion).

The carbamates include:

2-isopropoxyphenyl methylcarbamate (propoxur),

1-naphthyl N-methylcarbamate (carbaryl).

The synthetic pyrethroids include compounds of the formula I

in which

R¹ and R² represent halogen, optionally halogen-substituted alkyl oroptionally halogen-substituted phenyl,

R³ represent hydrogen or CN,

R⁴ represents hydrogen or halogen and

R⁵ represents hydrogen or halogen,

Preferred synthetic pyrethroids are those of the formula I in which

R¹ represents halogen, in particular fluorine, chlorine or bromine,

R² represents halogen, in particular, fluorine, chlorine, bromine,trihalogenomethyl, phenyl or chlorophenyl,

R³ represents hydrogen or CN,

R⁴ represents hydrogen or fluorine and

R⁵ represents hydrogen.

Particularly preferred synthetic pyrethroids are those of the formula Iin which

R¹ represents chlorine,

R² represents chlorine, trifluoromethyl or p-chlorophenyl,

R³ represents CN,

R⁴ represents hydrogen or fluorine and

R⁵ represents hydrogen.

Compounds of the formula I which may be mentioned in particular arethose in which

R¹ represents chlorine,

R² represents chlorine, or p-chlorophenyl,

R³ represents CN,

R⁴ represents fluorine in the 4-position and

R⁵ represents hydrogen.

Compounds which may be mentioned specifically are:

(α-cyano-4fluoro-3-phenoxy)-benzyl3-[2-4-chlorophenyl)-2-chlorovinyl]-2,2-dimethyl-cyclopropanecarboxylate(flumethrin),

α-cyano (4-fluoro-3-phenoxy)-benzyl2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclo-propanecarboxylate (cyfluthrin)and its enantiomers and stereomers,

α-cyano-3-phenoxybenzyl(±)-cis,trans-3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropanecarboxylate(deltamethrin),

α-cyano-3-phenoxybenzyl2,2dimethyl-3-2,2-dichlorovinyl)cyclopropanecarboxy-late(cypermetiin),

3-phenoxybenzyl(±)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylate(permethrin),

αcyano-3-phenoxy-benzyl α-(p-Cl-phenyl)-isovalerate (fenvalerate) and

2-cyano-3-phenoxybenzyl2-(2-chloro-α,α,α-trifluoro-p-toluidino)-3-methylbutrate (fluvalinate).

The amidines include:

3-methyl-2-[2,4-dimethyl-phenylimino]-thiazoline,

2-(4-choro-2-methylphenylimino)-3-methylthiazolidine,

2-(4chloro-2-methylphenylimino)-3-(isobutyl-1-enyl)-thiazolidine and

1,5-bis-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene(amitraz).

The juvenile hormones or juvenile-hormone-like substances includesubstituted diaryl ethers, benzoylureas and triazine derivatives. Thejuvenile hormones and juvenile-hormone-like substances include, inparticular, compounds of the following formulae:

The substituted diaryl ethers include, in particular, substitutedalkoxydiphenyl ethers or -diphenylmethanes of the general formula I

where

R¹ represents hydrogen, halogen, alkyl, alkoxy, alkylthio,halogenoalkyl, halogenoalkoxy, halogenoalkylthio, dioxyalkylene,dioxyhalogenoalkylene, CN, NO₂, alkenyl, alkinyl, alkoxyalkyl,alkoxyalkoxy or hydroxyalkoxy,

R² represents the radicals mentioned for R¹,

R³ represents the radicals mentioned for R¹,

R⁴ represents hydrogen, alkyl, halogenoalkyl or halogen,

R⁵ represents the radicals mentioned for R⁴,

Het represents optionally substituted heteroaryl which is not bonded tothe rest of the radical via the heteroatom,

X and Y independently of one another represent —O— or —S—,

Z represents —O—, —S—, —CH₂—, —CHCH₃— or —C(CH₃)₂— and

m and n independently of one another represent 0, 1, 2 or 3, but theirsum is equal to or greater than 2.

Particularly preferred compounds of the formula I are those in which

R¹ represents hydrogen, methyl, trifluoromethyl, methoxy,trifluoromethoxy, chlorine or fluorine,

R² represents hydrogen,

R³ represents hydrogen, fluorine, chlorine or methyl,

R⁴ represents hydrogen or methyl,

R⁵ represents methyl, ethyl, trifluoromethyl or hydrogen,

Het represents pyridyl or pyridazinyl which are optionally substitutedby fluorine, chlorine, methyl, NO₂, methoxy or methylmercapto,

X represents O,

Y represents O,

Z represents O, CH₂ or —(CH₃)₂—,

m represents 1 and

n represents 1.

The following compounds may be mentioned specifically:

R¹ R³ R⁵ R⁶ Z H H CH₃ H O H H CH₃ 2-Cl O 5-F H CH₃ H O H H CF₃ H O H HC₂H₅ H O H H H H O H H CH₃ H CH₂ H H CH₃ H C(CH₃)₂

The benzoylureas include compounds of the formula (V):

where

R¹ represents halogen,

R² represents hydrogen or halogen,

R³ represents hydrogen, halogen or C₁₋₄-alkyl and

R⁴ represents halogen, 1-5-halogeno-C₁₋₄-alkyl, C₁₋₄-alkoxy,1-5-halogeno-C₁₋₄-alkoxy C₁₋₄-alkylthio, 1-5-halogeno-C₁₋₄-alkylthio,phenoxy or pyridyloxy, it being possible for these to be substituted byhalogen, C₁₋₄-alkyl, 1-5-halogeno-C₁₋₄-alkyl, C₄-alkoxy,1-5-halogeno-C₁₋₄-alkoxy, C₁₋₄-alkylthio or 1-5-halogeno-C₁₋₄-alkylthio.

The following compounds may be mentioned in particular:

R¹ R² R⁴ H Cl CF₃ Cl Cl CF₃ F F CF₃ H F CF₃ H Cl SCF₃ F F SCF₃ H F SCF₃H Cl OCF₃ F F OCF₃ H F OCF₃ F F

F F

F F

The triazines include compounds of the formula (VI)

where

R¹ represents cyclopropyl or isopropyl;

R² denotes hydrogen, halogen, C₁-C₁₂-alkylcarbonyl, cyclopropylcarbonyl,C₁-C₁₂-alkylcarbamoyl, C₁-C₁₂-alkylthiocarbamoyl orC₂-C₆-alkenylcarbamoyl; and

R³ represents hydrogen, C₁-C₁₂-alkyl, cyclopropyl, C₂-C₆-alkenyl,C₁-C₁₂-alkylcarbonyl, cyclopropylcarbonyl, C₁-C₁₂-alkylcarbamoyl,C₁-C₁₂-alkyltiocarbamoyl or C₂-C₆-alkenylcarbamoyl, and their acidaddition salts which are non-toxic to warm-blooded species.

Compounds which may be mentioned in particular are:

R₁ R₂ R₃ Cyclopropyl H H Cyclopropyl H CH₃ Cyclopropyl H C₂H₅Cyclopropyl H C₃H₇-n Cyclopropyl H C₄H₉-n Cyclopropyl H C₅H₁₁-nCyclopropyl H C₆H₁₃-n Cyclopropyl H C₇H₁₅-n Cyclopropyl H C₈H₁₇-nCyclopropyl H C₁₂—H₂₅-n Cyclopropyl H CH₂—C₄H₉-n Cyclopropyl HCH₂CH(CH₃)C₂H₅ Cyclopropyl H CH₂CH═CH₂ Cyclopropyl Cl C₂H₅ CyclopropylCl C₆H₁₃-n Cyclopropyl Cl C₈H₁₇-n Cyclopropyl Cl C₁₂H₂₅-n Cyclopropyl HCyclopropyl Cyclopropyl H COCH₃ Cyclopropyl H COCH₃ HCl Cyclopropyl HCOC₂H₅ HCl Cyclopropyl H COC₂H₅ Cyclopropyl H COC₃H₇-n Cyclopropyl HCOC₃H₇-i Cyclopropyl H COC₄H₉-t HCl Cyclopropyl H COC₄H₉-n Cyclopropyl HCOC₆H₁₃-n Cyclopropyl H COC₁₁—H₂₃-n Cyclopropyl COCH₃ COC₂H₅ CyclopropylCOC₃H₇-n COC₆H₁₃-n Cyclopropyl COCH₃ COC₃H₇-n Cyclopropyl COC₂H₅COC₃H₇-n Cyclopropyl H COCyclopropyl Cyclopropyl COCyclopropylCOCyclopropyl Cyclopropyl COCH₃ COCH₃ Isopropyl H H Isopropyl H COCH₃Isopropyl H COC₃H₇-n Cyclopropyl H CONHCH₃ Cyclopropyl H CONHC₃H₇-iCyclopropyl CONHCH₃ CONHCH₃ Cyclopropyl H SCNHCH₃ Cyclopropyl HCONHCH₂CH═CH₂ Cyclopropyl CONHCH₂CH═CH₂ CONHCH₂CH═CH₂ CyclopropylCSNHCH₃ CSNHCH₃

The active compounds having the common names propoxur, cyfluthrin,flumethrin, pyriproxyfen, methoprene, diazinon, amitraz and levamisolmay be singled out in particular.

The shaped articles can furthermore comprise the additives customary forplastics. Customary additives are, for example, pigments, stabilizers,flow agents, glidants and mould release agents.

In the examples which follow,1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinium (common nameimidacloprid) is employed as active compound.

EXAMPLE 1

SC (Suspension concentrate) formulation: 368 g of imidacloprid 35 g ofblock copolymer of emulsifier ethylene oxide and propylene oxide 12 g ofditolyl ether sulphonate/formaldehyde condensate (emulsifier) 3.5 g ofwater-soluble polyvinyl alcohol 58.0 g of NH₄Cl 116.0 g of urea 1.2 g of(37% strength aqueous hydrochloric acid) 4.6 g of xanthan gum 560.5 g ofdistilled water

EXAMPLE 2

WP (dispersible powder) formulation 25.0 g of imidacloprid 1.0 g ofdiisobutyl-naphthalene-Na-sulphonate 10.0 g of n-dodecylbenzylsulphonicacid calcium 12.0 g of highly disperse silica-containing alkylarylpolyglycol ether 3.0 g of ditolyl ether sulphonate/formaldehydecondensate (emulsifier) 2.0 g of ® Baysilon-E, a silicone-containingantifoam by Bayer AG 2.0 g of finely disperse silicon dioxide and 45.0 gof kaolin

EXAMPLE 3

SL (water-soluble concentrate) formulation 18.3 g of imidacloprid 2.5 gof neutral emulsifier based on alkylaryl polyglycol ethers 3.5 g ofsodium diisooctyl sulphosuccinate 38.4 g of dimethyl sulphoxide and 37.5g of 2-propanol

EXAMPLE 4

SL (water-soluble concentrate) formulation 185 g of imidacloprid 5.0 gof sodium diisooctyl sulphosuccinate and 76.5 g of dimethyl sulphoxide

are added to a 100 g shampoo formulation composed of

44.4% by weight of Marlon AT 50, a triethanolamine salt ofalkylbenzenesulphonic acids by Hüls AG 11.1% by weight of Marlon AT 350,sodium salt of alkylbenzenesulphonic acids by Hüls AG  3.0% by weight ofcondensation product of oleic acids and diethanolamine by Hüls AG and41.5% by weight of polyethylene glycol.

EXAMPLE 5

Spray formulation composed of  2.0 g of imidacloprid 10.0 g of dimethylsulphoxide 35.0 g of 2-propanol and 53.0 g of acetone

EXAMPLE 6

Pour-on formulation 20.3 g of imidacloprid  1.8 g of polyvinyl alcohol 1.8 g of block copolymer based on ethylene oxide and propylene oxide0.26 g of xanthan gum  9.0 g of glycerol 59.2 g of distilled water

EXAMPLE 7

Composition: imidacloprid 10.00 g  di-n-butyl adipate 21.10 g diethylhexyl phthalate 9.10 g epoxidised soybean oil 2.30 g stearic acid0.80 g PVC 56.70 g 

Preparation: A mixture of di-n-butyl adipate, diethylhexyl phthalate andepoxidised soybean oil is added to a homogeneous mixture of imidaclopridand PVC in a mixer. Mixing is continued until the mixture ishomogeneous. If the mixture is heated during the mixing process, e.g. byincreasing the number of revolutions of the mixer, the plasticisermixture is more readily incorporated into the PVC. After the sub-sequenthomogeneous distribution of the stearic acid the mixture isinjection-moulded to form dog collars.

EXAMPLE 8

Composition: imidacloprid 10.00 g epoxidised soybean oil  2.30 g stearicacid  0.80 g acetyltributyl citrate 30.20 g PVC 56.70 g

Preparation: The mixture of acetyltributyl citrate and epoxidisedsoybean oil is applied to a homogeneous mixture of imidacloprid and PVCin a mixer. If the mixture is heating during the mixing process theplasticiser mixture is more readily incorporated into the PVC; mixing iscontinued until the mixture is homogeneous. The mixture is extruded toform dog collars by a conventional method.

EXAMPLE 9

Composition imidacloprid 20.00 g epoxidised soybean oil  2.30 g stearicacid  0.80 g acetyltributyl citrate 30.20 g PVC 46.70 g

Preparation: as in Example 8

EXAMPLE 10

Composition imidacloprid  7.50 g epoxidised soybean oil 10.00 g stearicacid  0.80 g acetyltributyl citrate 15.00 g PVC 66.70 g

Preparation: as in Example 8

EXAMPLE 11

Composition imidacloprid 10.00 g epoxidised soybean oil  2.30 g stearicacid  0.80 g triacetin 15.00 g PVC 71.90 g

Preparation: The mixture of triacetin and soybean oil is applied to thehomogeneous mixture of PVC and imidacloprid in a mixer. If the mixtureis heated, for example by increasing the number of revolutions of themixer, the plasticiser is more readily incorporated into the PVC. Afteradding stearic acid homogeneously, the mixture is extruded into sheetsin an extruder, from which medallions (=attachments for collars) arepunched.

EXAMPLE 12

Composition imidacloprid  5.00 g polyether block amide (Pebax ®) 94.50 g

Preparation: The active compound is applied to the substrate in ahigh-power mixer and the mixture is injection-moulded to form dogcollars.

EXAMPLE 13

Composition imidacloprid 10.00 g medium-chain triglycerides 15.00 ghighly dispersed silicon dioxide  0.50 g polyether block amide (Pebax ®)74.50 g

Preparation: Medium-chain triglycerides are applied to the homogeneousmixture of imidacloprid and the polyether block amide in a mixer. If themixture is heated the medium-chain triglycerides are more readilyincorporated into the polyether block amide. To improve flowabilityhighly dispersed silicon dioxide is added homogeneously before extrudingthe mixture. Sheets are extruded from which medallions (=attachments forcollars) are punched.

EXAMPLE 14

Composition imidacloprid 10.00 g styrene-butylene block copolymer 90.00g (Thermolast ® K)

Preparation: The active compound is applied to the substrate in ahigh-power mixer and the mixture is injection-moulded to form collars.

EXAMPLE 15

Composition imidacloprid  5.00 g copolyester (Hytrel ®) 95.00 g

Preparation: The mixture is extruded to form dog collars by aconventional method.

EXAMPLE 16

Composition imidacloprid 10.00 g polyether block amide (Pebax ®) 90.00 g

Preparation: The homogeneous mixture is extruded into sheets in anextruder, from which medallions (=attachments for collars) are punched.

EXAMPLE 17

Composition imidacloprid 10.00 g medium-chain triglycerides 30.00 ghighly dispersed silicon dioxide  0.50 g polyether block amide (Pebax ®)59.50 g

Preparation: as in Example 13

EXAMPLE A

1 ml of the SC formulation described in Example 1 was applied in theform of a pour-on solution to the shoulder of a dog infested with 200fleas. The test animal was immediately freed from adult fleas. Thetreatment according to the invention results in a 100% mortality rate ofthe fleas.

USE EXAMPLE A

1 ml of the formulation described in Example 1 was diluted in 11 ofwater, and this solution was poured over dogs which were infested withfleas until the dogs were dripping wet. The following results wereobtained:

Number of fleas per dog % Period Day untreated treated Action −1Infestation with 100 fleas 0 Treatment and counting 30 0 100 5, 8Infestation with 100 fleas 9 Counting 56 0 100 15 Infestation with 100fleas 16 Counting 76 0 100 19 Infestation with 100 fleas (untreatedanimals) 250 fleas (treated animals 20 Counting 39 0 100 26 Infestationwith 100 fleas 27 Counting 43 0 100

USE EXAMPLE B

1 ml of the solution in accordance with Example 1 were applied to a doesshoulder. 2 and 6 days after the treatment, the animal was infested with200 fleas. In each case on day 3 and day 7 after the treatment, thefleas remaining on the dogs were counted. No live fleas were found. A100% action was obtained.

What is claimed is:
 1. A method for non-systemically controlling aparasitic insect selected from fleas and lice on a human or animal, saidmethod comprising contacting said parasitic insect with an effectiveamount therefor of a compound of the formula:

wherein n represents 1 or 2; Subst. represents halogen; A and Z togetherwith the nitrogen and carbon atom to which they are bonded form asaturated heterocyclic ring having 6 ring members, said heterocyclicring containing in addition to the nitrogen atom to which A is bonded afurther 2 identical or different hetero groups, said hetero groups beingselected from N—H and N-alkyl, wherein the alkyl of said N-alkyl has 1to 4 carbon atoms; E represents NO₂ or CN; and X represents —CH═ or —N═;wherein said contacting of said parasitic insect with said compound iseffected by: a) topically applying said compound to the dermis of saidhuman or animal; or b) contacting the dermis of said human or animalwith an article containing said compound.
 2. The method according toclaim 1, which comprises contacting said parasitic insect with acompound selected from the group consisting of:

and


3. The method according to claim 1, wherein the animal is a dog or a catinfested with fleas.
 4. The method according to claim 3, wherein saidcontacting is effected by applying said compound topically to the dermisof said dog or cat by a pour-on or spot-on method.
 5. The methodaccording to claim 3, wherein said contacting is effected by contactingthe dermis of said dog or cat with an article containing said compound.6. The method according to claim 1, which is carried out on a human, andthe human is infected with lice.